Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings PowerPoint ® Lecture Presentations for Biology Eighth Edition Neil Campbell.

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Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings PowerPoint ® Lecture Presentations for Biology Eighth Edition Neil Campbell and Jane Reece Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp Chapter 11 Cell Communication

Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes The concentration of signaling molecules allows bacteria to detect population density Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

#1 AUTOCRINE SIGNALLING Cells produce and react to their own signaling. -T cells multiply in response to germs - Cell cycle advances in response to CdK - Bacteria can and some fungi can detect density

Fig Individual rod- shaped cells Spore-forming structure (fruiting body) Aggregation in process Fruiting bodies 0.5 mm 1 3 2

# 2 PARACRINE SIGNALING Signals released from a cell act upon target cells within an immediate vicinity. This can be In Extracellular fluid or Directly between cells

Local Animal and plant cells have cell junctions that directly connect the cytoplasm of adjacent cells Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig Plasma membranes Gap junctions between animal cells (a) Cell junctions Plasmodesmata between plant cells (b) Cell-cell recognition

example 1 Receptor  factor a factor a   a Exchange of mating factors Yeast cell, mating type a Yeast cell, mating type  Mating New a/  cell a/  1 2 3

In many other cases, animal cells communicate using local regulators, messenger molecules that travel only short distances Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 11-5ab Local signaling Target cell Secretory vesicle Secreting cell Local regulator diffuses through extracellular fluid (a) Paracrine signaling (b) Synaptic signaling Target cell is stimulated Neurotransmitter diffuses across synapse Electrical signal along nerve cell triggers release of neurotransmitter

#3 LONG DISTANCE SIGNALING

Fig. 11-5c Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream to target cells Target cell (c) Hormonal signaling

The Three Stages of Cell Signaling: A Preview Earl W. Sutherland discovered how the hormone epinephrine acts on cells Sutherland suggested that cells receiving signals went through three processes: – Reception – Transduction – Response Animation: Overview of Cell Signaling Animation: Overview of Cell Signaling Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig EXTRACELLULAR FLUID Plasma membrane CYTOPLASM Receptor Signaling molecule Relay molecules in a signal transduction pathway Activation of cellular response TransductionResponse 2 3 Reception 1

Evolution of Cell Signaling A signal transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response. Reception Transduction Response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Concept 11.2: Reception: A signal molecule binds to a receptor protein, causing it to change shape The binding between a signal molecule (ligand) and receptor is highly specific A shape change in a receptor is often the initial transduction of the signal Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

NOTE: There are 2 types of signal hormones:Steroids and non-steroids(proteins) The next slides will be on protein hormone ligands.

Receptors in the Plasma Membrane Most water-soluble protein signal molecules bind to specific sites on receptor proteins in the plasma membrane There are three main types of membrane receptors: – G protein-coupled receptors – Receptor tyrosine kinases – Ion channel receptors Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

A G protein-coupled receptor is a plasma membrane receptor that works with the help of a G protein The G protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 11-7b G protein-coupled receptor Plasma membrane Enzyme G protein (inactive) GDP CYTOPLASM Activated enzyme GTP Cellular response GDP P i Activated receptor GDP GTP Signaling molecule Inactive enzyme

Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines A receptor tyrosine kinase can trigger multiple signal transduction pathways at once Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 11-7c Signaling molecule (ligand) Ligand-binding site  Helix Tyrosines Tyr Receptor tyrosine kinase proteins CYTOPLASM Signaling molecule Tyr Dimer Activated relay proteins Tyr P P P P P P Cellular response 1 Cellular response 2 Inactive relay proteins Activated tyrosine kinase regions Fully activated receptor tyrosine kinase 6 6 ADP ATP Tyr P P P P P P

A ligand-gated ion channel receptor acts as a gate when the receptor changes shape When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na + or Ca 2+, through a channel in the receptor Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 11-7d Signaling molecule (ligand) Gate closed Ions Ligand-gated ion channel receptor Plasma membrane Gate open Cellular response Gate closed 3 2 1

Intracellular Receptors Some receptor proteins(for steroids) are intracellular, found in the cytosol or nucleus of target cells Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig Hormone (testosterone) Receptor protein Plasma membrane EXTRACELLULAR FLUID DNA NUCLEUS CYTOPLASM

Fig Receptor protein Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Hormone- receptor complex DNA NUCLEUS CYTOPLASM

Fig Hormone (testosterone) EXTRACELLULAR FLUID Receptor protein Plasma membrane Hormone- receptor complex DNA NUCLEUS CYTOPLASM

Fig Hormone (testosterone) EXTRACELLULAR FLUID Receptor protein Plasma membrane Hormone- receptor complex DNA mRNA NUCLEUS New protein CYTOPLASM

Concept 11.3: Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell Signal transduction usually involves multiple steps Multistep pathways can amplify a signal: A few molecules can produce a large cellular response Multistep pathways provide more opportunities for coordination and regulation of the cellular response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Protein Phosphorylation and Dephosphorylation In many pathways, the signal is transmitted by a cascade of protein phosphorylations Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig Signaling molecule Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP ADP Active protein kinase 2 P P PP Inactive protein kinase 3 ATP ADP Active protein kinase 3 P P PP i ATP ADP P Active protein PP P i Inactive protein Cellular response Phosphorylation cascade i

Fig Reception Transduction Response Binding of epinephrine to G protein-coupled receptor (1 molecule) Inactive G protein Active G protein (10 2 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (10 2 ) ATP Cyclic AMP (10 4 ) Inactive protein kinase A Active protein kinase A (10 4 ) Inactive phosphorylase kinase Active phosphorylase kinase (10 5 ) Inactive glycogen phosphorylase Active glycogen phosphorylase (10 6 ) Glycogen Glucose-1-phosphate (10 8 molecules)

Fine-Tuning of the Response Multistep pathways have two important benefits: – Amplifying the signal (and thus the response) – Contributing to the specificity of the response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The Specificity of Cell Signaling and Coordination of the Response Different kinds of cells have different collections of proteins These different proteins allow cells to detect and respond to different signals Even the same signal can have different effects in cells with different proteins and pathways Pathway branching and “cross-talk” further help the cell coordinate incoming signals Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig Signaling molecule Receptor Relay molecules Response 1 Cell A. Pathway leads to a single response. Response 2 Response 3 Cell B. Pathway branches, leading to two responses. Response 4 Response 5 Activation or inhibition Cell C. Cross-talk occurs between two pathways. Cell D. Different receptor leads to a different response.

Concept 11.5: Apoptosis (programmed cell death) integrates multiple cell-signaling pathways Apoptosis is programmed or controlled cell suicide A cell is chopped and packaged into vesicles that are digested by scavenger cells Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig µm

Apoptosis in the Soil Worm Caenorhabditis elegans Apoptosis is important in shaping an organism during embryonic development The role of apoptosis in embryonic development was first studied in Caenorhabditis elegans In C. elegans, apoptosis results when specific proteins that “accelerate” apoptosis override those that “put the brakes” on apoptosis Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Apoptotic Pathways and the Signals That Trigger Them Caspases are the main proteases (enzymes that cut up proteins) that carry out apoptosis Apoptosis can be triggered by: – An extracellular death-signaling ligand – DNA damage in the nucleus – Protein misfolding in the endoplasmic reticulum Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Apoptosis evolved early in animal evolution and is essential for the development and maintenance of all animals Apoptosis may be involved in some diseases (for example, Parkinson’s and Alzheimer’s); interference with apoptosis may contribute to some cancers Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig Interdigital tissue 1 mm

Fig. 11-UN1 Reception Transduction Response Receptor Relay molecules Signaling molecule Activation of cellular response 1 2 3

You should now be able to: 1.Describe the nature of a ligand-receptor interaction and state how such interactions initiate a signal-transduction system 2.Compare and contrast G protein-coupled receptors, tyrosine kinase receptors, and ligand- gated ion channels 3.List two advantages of a multistep pathway in the transduction stage of cell signaling 4.Explain how an original signal molecule can produce a cellular response when it may not even enter the target cell Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

5.Define the term second messenger; briefly describe the role of these molecules in signaling pathways 6.Explain why different types of cells may respond differently to the same signal molecule 7.Describe the role of apoptosis in normal development and degenerative disease in vertebrates Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings